Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II.
The macrophage scavenger receptor, which has been implicated in the pathogenesis of atherosclerosis, has an unusually broad binding specificity. Ligands include modified low-density lipoprotein and some polyanions (for example, poly(I) but not poly(C]. The scavenger receptor type I (ref. 3) has three principal extracellular domains that could participate in ligand binding: two fibrous coiled-coil domains (alpha-helical coiled-coil domain IV and collagen-like domain V), and the 110-amino-acid cysteine-rich C-terminal domain VI. We have cloned complementary DNAs encoding a second scavenger receptor which we have termed type II. This receptor is identical to the type I receptor, except that the cysteine-rich domain is replaced by a six-residue C terminus. Despite this truncation, the type II receptor mediates endocytosis of chemically modified low-density lipoprotein with high affinity and specificity, similar to that of the type I receptor. Therefore one or both of the extracellular fibrous domains are responsible for the unusual ligand-binding specificity of the receptor.
Rohrer
L
L
Department of Biology, Massachusetts Institute of Technology, Cambridge 02168.
Freeman
M
M
Kodama
T
T
Penman
M
M
Krieger
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004705:Endocytosis; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000032:analysis*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013329:Structure-Activity Relationship; D014162:Transfection
D004247:DNA; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D000071228:Polyelectrolytes; D011108:Polymers; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; C454739:Scarb1 protein, mouse; C032629:acetyl-LDL